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Trial registered on ANZCTR


Registration number
ACTRN12620001104943
Ethics application status
Approved
Date submitted
2/10/2020
Date registered
26/10/2020
Date last updated
10/05/2021
Date data sharing statement initially provided
26/10/2020
Date results information initially provided
10/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single Dose Study to Determine the Safety and Tolerability of Intranasal REVTx-99 in Healthy Adult Volunteers
Scientific title
A Phase 1, Placebo-Controlled, Single Dose, Escalating Dose Study to Determine the Safety and Tolerability of Intranasal REVTx-99 in Healthy Adult Volunteers
Secondary ID [1] 302354 0
RVL-NHV01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
SARS-CoV-2 (COVID-19) 319133 0
Condition category
Condition code
Infection 317097 317097 0 0
Other infectious diseases
Respiratory 317365 317365 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study consists of 5 single dose cohorts and 1 multiple dose cohort which will be studied sequentially. Participants in each single dose cohort will receive a single dose of either placebo or 5 mcg, 15 mcg, 30 mcg, 50 mcg or 100 mcg of REVTx-99 intranasally. Participants in the multiple dose cohort will receive 100 mcg of REVTx-99 intranasally every day for 5 days. Study drug will be administered by a registered nurse.
Intervention code [1] 318643 0
Prevention
Comparator / control treatment
Placebo: 5% v/v ethanol in saline
Control group
Placebo

Outcomes
Primary outcome [1] 325181 0
To determine the Safety and Tolerability of a single and multiple intranasal doses of REVTx-99 when administered to healthy adults as assessed by the collection of safety data, such as adverse events, clinical laboratory tests, vital signs, 12-lead ECGs and Physical Exams. The clinical laboratory tests to assess safety are as follows: Haematology: Haematocrit, Haemoglobin, Platelet count, White blood cell count and Red blood cell count. Clinical Chemistry: Serum creatinine, Uric Acid, Calcium, Total Protein, Alkaline phosphatase, Urea, Total Bilirubin, Chloride, Bicarbonate, Albumin, Sodium, Potassium, Plasma Glucose, ALT, AST and LDH.
Timepoint [1] 325181 0
Single Dose: Continuously from Day 1/Predose through to Day 8/Hour 168 - End-of-Study (EOS)

Multiple Dose: Continuously from Day 1/Predose through to Day 12 - End-of-Study (EOS)
Primary outcome [2] 325182 0
To determine the pharmacodynamic (PD) effect of REVTx-99 in healthy adult volunteers as measured by nasal cytokine levels.

Nasal cytokines that will be measured include: IP-10, IL-6, IFN-alpha, IFN-beta, IFN-gamma
Timepoint [2] 325182 0
Single Dose: Nasal mucosa cytokine levels will be measured at Day 1/Predose and postdose at Hours 10-12; Day 2/Hours 20-24; Day 3/Hours 40-50 and Day 8 (EOS)

Multiple Dose: Nasal mucosa cytokine levels will be measured at Day 1-5/Predose and Day 12 (EOS)
Secondary outcome [1] 387104 0
To evaluate the change in serum cytokine levels from Screening through EOS.

Serum cytokines that will be measured include: IP-10, IL-6, IFN-alpha, IFN-beta, IFN-gamma
Timepoint [1] 387104 0
Single Dose: Serum Cytokine levels will be measured at Screening and on Day 1/ Predose, Day 1/ Hour 6 and Day 2/ Hour 24 for all cohorts. All timepoints plus Day 3/Hour 48 and Day 8/Hour 168 (EOS) will be measured for Cohort 4 and 5.

Multiple Dose: Serum cytokine levels will be measured at Screening and Days 1-5/Pre-dose and on Day 12 (EOS)
Secondary outcome [2] 387105 0
To evaluate treatment-emergent adverse events (TEAEs) from Day 1/Hour 0 through to End of Study (EOS).
Timepoint [2] 387105 0
Single Dose: Adverse events will be assessed continuously from Day 1 through to Day 8- End Of Study (EOS). Adverse event data will be collected by participant self-report as well as any observed abnormalities in vital signs, 12-lead ECG parameters, clinical laboratory values or any other safety assessment.

Multiple Dose: Adverse events will be assessed continuously from Day 1 through to Day 12- End Of Study (EOS). Adverse event data will be collected by participant self-report as well as any observed abnormalities in vital signs, 12-lead ECG parameters, clinical laboratory values or any other safety assessment.
Secondary outcome [3] 387794 0
Exploratory outcome: To evaluate the Pharmacokinetic (PK) properties of a single and multiple doses of RVL-NHV01 in healthy participants. PK parameters to be assessed include: - Half-life (T1/2) - Time to Maximum Concentration (Tmax) - Maximum peak observed concentration (Cmax) - The magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel) - Area under the concentration-time curve from Hour 0 through the last quantifiable concentration time (AUClast) - Area under the concentration-time from 0 to infinity AUC0-8
Timepoint [3] 387794 0
Single dose: PK serum samples will be taken for all cohorts at the following timepoints: Day 1/Pre-dose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours and 12 hours post-dose, Day 2 Additional PK serum samples will be taken for Cohort 4 and 5 only at the following timepoints: Day 3/Hour 48 and Day 8/Hour 168 (EOS).

Multiple Dose: PK serum samples will be taken at Day 1-5/Predose and Day 12 (EOS)

Eligibility
Key inclusion criteria
1. Participant must be a healthy, adult volunteers, 18-50 years of age, inclusive at Screening.
2. Participant must test negative for influenza; and SARS-CoV-2 by RT-PCR at Screening
and should be performed no more than 1 week prior to dosing.
3. Participant must be willing and able to provide written informed consent.
4. Participant must be a nonsmoker, nontobacco user and non-nicotine product user or a
former smoker/user. (has not smoked, vaped or used tobacco/nicotine products in the 6
months prior to dosing).
5. Participant must have a Body Mass Index (BMI) more than or equal to 18.0 kg/M2 and less than or equal to 30.0 kg/M2
6. Female participants must be of non-childbearing potential or using a medically
acceptable contraceptive regimen from Screening until 30 days post-dose.
7. Male participants must be surgically sterile or using a medically acceptable
contraceptive regimen, from screening until 90 days post-dose.
8. Participant must be willing and able to comply with the study schedule,
restrictions, and requirements.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participants with a concomitant disease, disability, or condition which may interfere
with the conduct of the study, or which would, in the opinion of the Investigator, pose
an unacceptable risk to the participants in this study, including, but not limited to
alcohol dependency or abuse, drug dependency or abuse, or previously diagnosed
psychiatric disease.
2. Participants who have a history of Bell’s palsy.
3. Participants who give a verbal history of risk factors for SARS-CoV-2 and other
common viral respiratory infections including, but not limited to, pre-existing
pulmonary disease such as asthma, reactive airway disease, chronic obstructive
pulmonary disease, pulmonary hypertension, and emphysema.
4. Participants who give a verbal history of being immunocompromised due to disease or
medication (e.g. cancer immunosuppressive therapy), hypertension, coronary artery
disease with history of stent or graft, heart failure NYHA class 2 or greater, or
diabetes.
5. Participants who have used any prescription medications within 14 days or over-the-
counter medications within 7 days before study drug dosing, with the exception of contraceptives for female participants and occasional paracetamol use (at the discretion
of the Investigator).
6. Participants who have used vitamins, dietary or herbal supplement, or nutritional
supplement within 7 days before study drug dosing.
7. Participant has a history of chronic sinusitis requiring regular use of nasal spray.
8. Participant has had recent nasal surgery or invasive nasal or dental procedure in the
preceding 28 days of Day -1.
9. Participant has had active allergic rhinitis within 14 days prior to administration of first
dose of Investigational Product.
10. Participant has had administration of systemic antibiotics or antivirals within 7 days
prior to Screening (excluding topical/external use of antibiotics).
11. Participant has had major surgery within 30 days of Day -1.
12. Pregnant or breast-feeding women.
13. Participant has received of any immunoglobulins and/or blood products within 3
months of study Screening.
14. Participant has had acute respiratory illness within 30 days prior to administration
of first dose of Investigational Product.
15. Participant has used or been administered any intranasal medication or nasal
topical treatment within 30 days of Day -1, or plan to use any nasal products during the study.
16. Participant is using systemic corticosteroids including low-dose oral prednisone
and any systemic immunomodulatory therapy.
17. Participant has received treatment with any investigational product in any clinical
study within 30 days of Day -1 or five half-lives, whichever is longer.
18. Participant has received a vaccination within 30 days of dosing
19. Participant is unwilling or unable to comply with the study protocol requirements.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An unblinded statistician will prepare a Randomization Schedule which will be provided to the site in a blinded manner in order to allocate the treatment assignment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerised randomisation schedule will be created by a statistician who is not otherwise involved in the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
The sample size was determined by practical considerations and is not based on statistical
power calculations.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 17591 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 31335 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 306786 0
Commercial sector/Industry
Name [1] 306786 0
Revelation Biosciences
Address [1] 306786 0
Revelation Biosciences, Inc.
350 Sharon Park Drive, R4
Menlo Park, CA. 94025
Country [1] 306786 0
United States of America
Primary sponsor type
Other
Name
Linear Clinical Research Ltd
Address
Level 1, B Block
Hospital Ave
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 307337 0
Commercial sector/Industry
Name [1] 307337 0
Revelation Biosciences
Address [1] 307337 0
Revelation Biosciences, Inc.
350 Sharon Park Drive, R4
Menlo Park, CA. 94025
Country [1] 307337 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306946 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 306946 0
123 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 306946 0
Australia
Date submitted for ethics approval [1] 306946 0
24/08/2020
Approval date [1] 306946 0
15/09/2020
Ethics approval number [1] 306946 0
2020-08-796

Summary
Brief summary
The purpose of this study is to assess the safety and tolerability of REVx-99, as well as the Pharmacokinetics (PK- how your body uses the study drug) and pharmacodynamics (PD - how the study drug carries out its actions on the body). We are doing this study in healthy men and women to find out:
- Does the drug have any side-effects and is it well tolerated when given as a single
dose?
- How much of the drug gets into the blood stream, and how long does the body take
to get rid of it?

This study will compare REVTx-99 with placebo. A placebo has no active drug in it. One group of participants will receive REVTx-99 and another group will receive the placebo. The effects seen in participants receiving the study drug will be compared to the effects seen in participants who receive placebo.

We will be testing a single dose of the study drug in up to 40 healthy volunteers who will be divided into 5 cohorts of 8 people each and testing multiple doses in a single cohort of 8 people. Each single dose cohort is planned to receive an increasing dose of REVTx-99.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105542 0
Dr Jasmine Williams
Address 105542 0
Linear Clinical Research
Level 1, B Block
Hospital Ave
Nedlands, WA 6009
Country 105542 0
Australia
Phone 105542 0
+61 8 63825100
Fax 105542 0
Email 105542 0
jwilliams@linear.org.au
Contact person for public queries
Name 105543 0
Ms Carol Odle
Address 105543 0
Revelation Biosciences, Inc.
350 Sharon Park Drive, R4
Menlo Park, CA. 94025
Country 105543 0
United States of America
Phone 105543 0
+1 760 703 2438
Fax 105543 0
Email 105543 0
codle@cgjtx.com
Contact person for scientific queries
Name 105544 0
Dr George Tidmarsh
Address 105544 0
Revelation Biosciences, Inc.
350 Sharon Park Drive, R4
Menlo Park, CA. 94025 USA
Country 105544 0
United States of America
Phone 105544 0
+1 650 208 3191
Fax 105544 0
Email 105544 0
gtidmarsh@cjgtx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary